This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas: I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing small molecular inhibitors targeted against HIV-1. Some notable scientific findings from our research program in 2001-2002 include: 1) the definition of loss of mitotic spindle checkpoint as a mechanism for HTLV-I transformation of cells and the characterization of mitotic spindle checkpoint components necessary for function; 2) the demonstration that a gain-of-function p53 mutant affects mitotic spindle checkpoint function; 3) the elucidation of HTLV-I Tax interaction with cyclin dependent kinase 4 in Rb phosphorylation; 4) the identification of a direct protein-protein interaction between HIV Tat co-factor cyclin T1 and Sp1 which is necessary for viral LTR-expression; 5) the characterization of a novel cellular RNA-helicase that cooperates with Rev for post-transcriptional HIV-1 gene expression; and 6) the discovery of several small molecules such as poly-arginine which can inhibit HIV-1 replication. Our research program helps advance the understanding of how HTLV-I causes human leukemia and how HIV-1 causes AIDS. Our research on the discovery of small molecules which may inhibit HIV-1 replication is aimed towards potentially contributing to the development of new drugs for HIV-1.